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Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fas-induced apoptosis in viraemic and HAART-controlled HIV-1-positive patients.
Antivir Ther. 2011; 16(7):1047-55.AT

Abstract

BACKGROUND

Recently, we identified increased rates of CD4(+) T-cell apoptosis in HCV-infected HIV-positive patients as a potential mechanism for enhanced mortality in patients with HIV/HCV coinfection. Since this effect might be attributed to changes in receptor-induced apoptosis, we studied expression and function of Fas ligand (FasL) and its death receptor Fas on CD4(+) T-cells in HIV/HCV coinfection.

METHODS

In this cross-sectional study, we simultaneously analysed surface expression of Fas and FasL on CD4(+) T-cells and serum levels of soluble FasL in HCV/HIV-coinfected, HIV-monoinfected and HCV-monoinfected patients. Susceptibility to FasL-induced apoptosis was analysed by incubating isolated peripheral blood mononuclear cells with rhFasL followed by measuring CD4(+) T-cell apoptosis.

RESULTS

HIV and HCV monoinfection were associated with significantly enhanced surface expression of Fas. Highest Fas expression was detected in HIV/HCV-coinfected patients and correlated with low CD4(+) T-cell counts. By contrast, elevated levels of soluble and cellular FasL were found only in patients with HIV infection, but not in patients with HCV infection. Importantly, enhanced Fas expression in HCV/HIV coinfection rendered CD4(+) T-cells more susceptible towards FasL-induced apoptosis. While effective HAART normalized expression and secretion of FasL in HIV-infected and HIV/HCV-coinfected patients, expression of Fas decreased only slightly and still remained significantly elevated as compared with healthy controls.

CONCLUSIONS

Our findings suggest a synergistic mechanism in HIV/HCV coinfection between up-regulation of Fas expression on CD4(+) T-cells and HIV-induced elevated levels of cellular and soluble FasL. Together, both effects contribute to enhanced apoptosis of CD4(+) T-cells in HIV/HCV coinfection.

Authors+Show Affiliations

Department of Internal Medicine I, University of Bonn, Bonn, Germany. christian.koerner@ukb.uni-bonn.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22024520

Citation

Körner, Christian, et al. "Hepatitis C Coinfection Enhances Sensitization of CD4(+) T-cells Towards Fas-induced Apoptosis in Viraemic and HAART-controlled HIV-1-positive Patients." Antiviral Therapy, vol. 16, no. 7, 2011, pp. 1047-55.
Körner C, Tolksdorf F, Riesner K, et al. Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fas-induced apoptosis in viraemic and HAART-controlled HIV-1-positive patients. Antivir Ther. 2011;16(7):1047-55.
Körner, C., Tolksdorf, F., Riesner, K., Krämer, B., Schulte, D., Nattermann, J., Rockstroh, J. K., & Spengler, U. (2011). Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fas-induced apoptosis in viraemic and HAART-controlled HIV-1-positive patients. Antiviral Therapy, 16(7), 1047-55. https://doi.org/10.3851/IMP1882
Körner C, et al. Hepatitis C Coinfection Enhances Sensitization of CD4(+) T-cells Towards Fas-induced Apoptosis in Viraemic and HAART-controlled HIV-1-positive Patients. Antivir Ther. 2011;16(7):1047-55. PubMed PMID: 22024520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fas-induced apoptosis in viraemic and HAART-controlled HIV-1-positive patients. AU - Körner,Christian, AU - Tolksdorf,Felix, AU - Riesner,Katarina, AU - Krämer,Benjamin, AU - Schulte,Daniela, AU - Nattermann,Jacob, AU - Rockstroh,Jürgen K, AU - Spengler,Ulrich, PY - 2011/10/26/entrez PY - 2011/10/26/pubmed PY - 2012/4/21/medline SP - 1047 EP - 55 JF - Antiviral therapy JO - Antivir Ther VL - 16 IS - 7 N2 - BACKGROUND: Recently, we identified increased rates of CD4(+) T-cell apoptosis in HCV-infected HIV-positive patients as a potential mechanism for enhanced mortality in patients with HIV/HCV coinfection. Since this effect might be attributed to changes in receptor-induced apoptosis, we studied expression and function of Fas ligand (FasL) and its death receptor Fas on CD4(+) T-cells in HIV/HCV coinfection. METHODS: In this cross-sectional study, we simultaneously analysed surface expression of Fas and FasL on CD4(+) T-cells and serum levels of soluble FasL in HCV/HIV-coinfected, HIV-monoinfected and HCV-monoinfected patients. Susceptibility to FasL-induced apoptosis was analysed by incubating isolated peripheral blood mononuclear cells with rhFasL followed by measuring CD4(+) T-cell apoptosis. RESULTS: HIV and HCV monoinfection were associated with significantly enhanced surface expression of Fas. Highest Fas expression was detected in HIV/HCV-coinfected patients and correlated with low CD4(+) T-cell counts. By contrast, elevated levels of soluble and cellular FasL were found only in patients with HIV infection, but not in patients with HCV infection. Importantly, enhanced Fas expression in HCV/HIV coinfection rendered CD4(+) T-cells more susceptible towards FasL-induced apoptosis. While effective HAART normalized expression and secretion of FasL in HIV-infected and HIV/HCV-coinfected patients, expression of Fas decreased only slightly and still remained significantly elevated as compared with healthy controls. CONCLUSIONS: Our findings suggest a synergistic mechanism in HIV/HCV coinfection between up-regulation of Fas expression on CD4(+) T-cells and HIV-induced elevated levels of cellular and soluble FasL. Together, both effects contribute to enhanced apoptosis of CD4(+) T-cells in HIV/HCV coinfection. SN - 2040-2058 UR - https://www.unboundmedicine.com/medline/citation/22024520/Hepatitis_C_coinfection_enhances_sensitization_of_CD4_+__T_cells_towards_Fas_induced_apoptosis_in_viraemic_and_HAART_controlled_HIV_1_positive_patients_ L2 - http://www.diseaseinfosearch.org/result/3332 DB - PRIME DP - Unbound Medicine ER -